tbuckley/cabot-search huggingface dataset:
Outcomes of cardiac tamponade in patients with lung cancer.
Authors: Pyi Phyo Aung, Kyeeun Park, Htoo Myat Nge
Journal: Journal of Clinical Oncology (2022)

e21083 Background: Cardiac tamponade is a serious complication of pericardial effusion and life-threatening cardio-oncological emergency. The prevalence of malignant pericardial effusion varies between 1% and 20% in autopsy studies. Primary lung cancer is the most common cause of metastatic tumor involving the pericardium. The common triggers for pericardial effusion in patients with lung cancer include cancer itself, chemotherapy and radiation therapy. The outcomes of cardiac tamponade in patients with lung cancer remain to be elucidated. Methods: We conducted a retrospective analysis of the 2016 to 2018 Nationwide Inpatient Sample. Adult patients with lung cancer and cardiac tamponade (age ≥ 18) were selected using the ICD-10 diagnosis code. Discharge-level weight analysis was used to produce a national estimate. A univariate and multivariable hierarchical regression analysis was performed to calculate the odds ratio (OR). Results: During the study period, 1,207,580 patients were admitted due to lung cancer of which 7,105 (0.6%) developed cardiac tamponade. Patients with cardiac tamponade tended to be younger (63.2 SE 0.3 vs 69.1 SE 0.2), male (54.5% vs 51.2%) and large proportion of radiation treatment (0.9% vs 0.7%), and smaller proportion of diabetes (18.5% vs 24.2%), chronic kidney disease (4.5% vs 7.6%) and heart failure (15.9% vs 16.2%). After adjusting for age, sex, comorbidity burden and heart failure, cardiac tamponade increased the risk for in-hospital mortality (OR 2.1; 1.9 – 2.5; p &lt; 0.001), major adverse cardiac events (OR 1.6; 1.3 – 2.1; p &lt; 0.001) and acute respiratory failure (OR 2.3; 2.0 – 2.5; p &lt; 0.001). Furthermore, cardiac tamponade was associated with longer length of stay (8.6 SE 0.2 vs 6.0 SE 0.01, p &lt; 0.001) and higher total hospital cost ($118,708.0 SE $4,027.1 vs $65,369.8 SE $170.6). Conclusions: In conclusion, patients with lung cancer who developed cardiac tamponade were associated with poor outcomes including higher in-hospital mortality, MACE, acute respiratory failure, a longer length of stay by 2.6 days, and higher cost of hospitalization. Cardiac tamponade was more common in males and patients who received radiation therapy. Further studies are warranted to develop an optimal management guideline for this cardio-oncological emergency.
An 11-gene expression signature related to tumorigenesis and immunosuppression in primary cutaneous melanoma predicts sentinel lymph node metastatic status.
Authors: Ahmad A. Tarhini, Brian Hobbs, Arjun Khunger, Ibrahim Yassine, Iyad Kobeissi, Patrick Hwu, Vernon K. Sondak, William LaFramboise, John M. Kirkwood
Journal: Journal of Clinical Oncology (2022)

e21579 Background: A biomarker derived from the primary melanoma tumor to predict regional sentinel lymph node (SLN) metastatic status can be valuable in guiding the decision making in planning the SLN surgical procedure for candidate patients. Methods: Gene expression profiling was performed on primary cutaneous melanoma tumor biopsies of 49 (24 known SLN+, 25 SLN-) patients (T3a/b, T4a/b) who underwent SLN for staging using transcriptome profiling analysis. U133A 2.0 Affymetrix gene chips were used. Significance Analysis of Microarrays (SAM) was used to test the association between gene expression level of the primary tumor and SLN status. Genes with fold change &gt; 1.5 and q value &lt; 0.05 were considered differentially expressed. Pathway analysis was performed using Ingenuity Pathway Analysis. Benjamini and Hochberg method was used to adjust for multiple testing in pathway analysis. All statistical analyses were implemented in R. Results: A total of 49 patients with primary cutaneous melanoma were studied, of which, 24 were diagnosed as SLN positive and 25 as SLN negative by routine H&amp;E and immunohistochemistry. Using SLN metastatic status as the outcome, a univariate logistic regression model was fitted with individual probe sets. A total of 251 probe sets were filtered and 11 probe sets were considered as differentially expressed (DE) between SLN-ve and SLN+ve groups, with the selection criterion set at Benjamini- Hochberg method -adjusted p -value below 0.05 and the absolute log fold change above 0.5. As each of the 11 probe sets was matched to a unique known gene, an 11 gene signature was derived and among them, the expression level of 7 genes was significantly reduced in the SLN+ve group compared to the SLN-ve group, while 4 genes were overexpressed in the SLN+ve group. Integrative and interactive heatmaps were produced from hierarchical cluster analysis to show the 11 differentially expressed genes. Selected genes were found to be uniformly related to tumorigenesis, malignant progression, DNA repair, cell cycle regulation, chemoresistance, immunosuppression and/or involvement in multiple cancer-related pathways. Several of the selected genes were previously shown to be prognostic in various malignancies. Conclusions: We present a unique 11-gene expression signature derived from primary melanoma tumor biopsy samples and related to tumorigenesis and immunosuppression that may be useful for the prognostic stratification of melanoma patients. This may allow the optimal selection of patients for SLN biopsy.
Genomic characterization of Chinese locally advanced or metastatic gastric cancer.
Authors: Xiaotian Zhang, Yakun Wang, Shi Xinying, Changsong QI, Zhi Peng, Tong Xie, Dan Liu, Siyuan Cheng, Panpan Zhang, Yiqun Zhang, Qianhui Wan, Nana Hu, Zhihua Pei, Dongliang Wang, Lin Shen
Journal: Journal of Clinical Oncology (2022)

e16085 Background: The comprehensive molecular characterization of gastric cancer has been uncovered by The Cancer Genome Atlas (TCGA) research work. However, the genomic feature of Chinese locally advanced or metastatic gastric cancer has been seldom reported. This study aims to explore the genomic landscape of Chinese locally advanced or metastatic gastric cancer. Methods: 556 locally advanced or metastatic gastric cancer patients were enrolled in this study and 245 eligible patients with adequate clinicopathological data were analyzed. The baseline tumor tissues and corresponding blood were collected and target-captured sequencing were applied. Both tumor fragments and fragmented genomic DNA were subjected to the NGS platform aiming a panel covering exon regions of 599 genes. Genetic alterations were analyzed to investigate the mutational profile of Chinese locally advanced or metastatic gastric cancer. Results: The top 10 common tumor driver gene alterations among all cases were TP53, ARID1A, CDH1, ARID1B, NOTCH1, ATRX, AR, RAD50, SMAD4 and ZFHX3. TP53 mutation was detected in 70% of all cases, which was significantly higher than that in the TCGA non-Asian (44%) and Asian (46%) advanced gastric cancer patients. 90% (20/22) MSI-H patients had high TMB values, and 32.7% (20/61) high TMB patients were MSI-H. Neither TMB values nor MSI scores was statistically different between patients with response (CR+PR) and without response (PD+SD) to chemotherapy (p = 0.366, 0.436). While the combination of SPTA1 and TP53 mutation was significantly more frequent in response (CR+PR) than non-response (PD+SD) patients. Conclusions: The mutated driver genes of Chinese locally advanced or metastatic gastric cancer were different from the TCGA advanced gastric cancer. The combination of TP53 and and SPTA1 could identify the patients’ response to chemotherapy.
When to de-intensify oncologic surveillance scheme for non-clear cell renal cell carcinoma
Authors: A. Martini, G. Colandrea, D. Cignoli, G. Rosiello, G. Fallara, G. Basile, L. Nocera, F. Belladelli, D. Canibus, C. Re, G. Musso, F. Cei, F. De Cobelli, G. Brembilla, A. Briganti, R. Bertini, A. Necchi, D. Raggi, F. Montorsi, A. Salonia, A. Larcher, U. Capitanio
Journal: European Urology (2022)
Characterization of time to diagnosis indicates shorter interval for screenable versus symptom-driven cancers.
Authors: Vladimir Gainullin, Jing Tong, Yali Li, Mudit Gupta, Braxton Lagerman, Jackie Blank, Paul J. Limburg, Christine Hathaway
Journal: Journal of Clinical Oncology (2022)

10526 Background: Cancer screening provides a straightforward diagnostic path compared to non-screening, which often requires complex evaluation for patients with non-specific symptoms. The time to diagnosis (from clinical presentation or screening event to definitive diagnosis) captures the clinical efficiency of the journey. The study characterizes time to diagnosis for cancers with and without USPSTF Grade A/B screening recommendations. This could inform the value of screening in diagnostic management and care efficiency improvements. Methods: The Geisinger Health System Phenomics Initiative Database provides deidentified EHR and tumor registry data. Patients aged 50-74 with encounters at least biennially for six years prior to a cancer diagnosis were frequency-matched to a non-cancer control group by diagnosis year. From 18 months prior to diagnosis, equally-sized random samples were drawn (with replacement) from a time-bounded sliding window at monthly intervals. Aggregated procedure and diagnostic code counts for cancer and non-cancer samples were used to calculate the Bray-Curtis dissimilarity (BCd) statistic. The start of the diagnostic path was defined as the earliest date with a monotonically-increasing statistically-significant difference in BCd (95% CI), and was stratified into cancers with and without screening and by stage. Results: 8188 new cancer cases were identified between 2010-2019; 40% had an established screening modality (breast, lung, colorectal, cervical), 55% of which were screened prior to diagnosis. The time to diagnosis for non-screenable cancers was 6 months versus 3 months for screenable cancers. The BCd for procedures differed by 0.029 (95% CI: 0.021-0.037) between the two groups at 6 months prior to diagnosis. Stages I and IV had a time to diagnosis of 3 months across all cancers versus 7 and 6 months for stages II and III, respectively. Conclusions: We report the first known quantification of time to diagnosis across multiple cancers. Screenable cancers were associated with shorter time to diagnosis than non-screenable cancers. Stage II and III cancers took longer to diagnose than stage I and IV, likely related to early detection by screening in the former and severe symptom presentation in the latter. These novel data highlight improved time to diagnosis as another achievable benefit from expanded, multi-cancer screening.
Survival outcomes following immune checkpoint inhibitor therapy of advanced cutaneous melanoma by age and tumor infiltrating lymphocytes in the primary cutaneous site.
Authors: Mallory Kane, Aaron N. Holmes, Phil Kerr, Upendra P. Hegde
Journal: Journal of Clinical Oncology (2022)

e21514 Background: Tumor infiltrating lymphocytes (TILs) in the tumor microenvironment generate anti-tumor immunity and are associated with response to immune checkpoint inhibitor (ICI) therapy of melanoma. However, likelihood of response to ICI therapy depends upon intensity of TILs, proportion of effector and regulatory T cells and age. Methods: In a research study approved by the Institutional Review Board of University of Connecticut, we retrospectively analyzed outcome of patients diagnosed with cutaneous melanoma between 2009 and 2019 and developed unresectable stage III or stage IV disease requiring ICI treatment. Patients were stratified by age (&lt; 75 and &gt; 75 years old) and TILs at the primary cutaneous melanoma site categorized as brisk (present throughout vertical phase), non-brisk (present in one of more foci of vertical phase) or absent. Patient’s age at the time of metastases, as well as 12-month and 24-month overall survival (OS) following ICI treatment was recorded. Results: A total of 93 patients were screened, and 68 were included for analysis of survival outcome. Patients had to receive at least one dose of ICI treatment at UConn Health and had available data on TILs of primary cutaneous melanoma. In patients over 75 years of age, those with brisk TILs had an increased 24-month survival compared to those with non-brisk or absent TILs (100% vs. 45%, p = 0.04). In patients &lt; 75 years of age, the 24 month survival was similar in those with brisk and non-brisk or absent TILs (67% vs. 69%, p = .91). There was no significant difference in overall survival between patients &lt; 75 or &gt; 75 years with brisk TILs (67% vs. 100%, p = .19). Additionally, in patients with non-brisk or absent TILs, there was a not quite significant difference in survival between those &gt; 75 vs &lt; 75 years (45% vs. 69%, p = .09). Conclusions: Our findings suggest that intensity of TILs in primary cutaneous melanoma is predictive of outcome following ICI treatment of advanced melanoma in patients over 75 years of age. These findings support possible interaction between qualitative differences of TILs and patient age. Our findings may help identify older melanoma patients who may benefit from ICI treatment.
Quality and content of online cancer information: An analysis of NCI-designated cancer center YouTube videos.
Authors: Luke Kim, Evelin Trejo, Dame Idossa, Narjust Duma, Ana I. Velazquez Manana
Journal: Journal of Clinical Oncology (2022)

11041 Background: The internet and social media have become a common source of medical information. Previous analyses have found that YouTube videos disseminate biased cancer related information of low to moderate quality. We analyzed online information disseminated by NCI-designated Cancer Centers (CC) through their YouTube pages. Methods: We searched CC websites and online search engines to identify CC-specific YouTube pages. Our sample included each CC’s top 20 most-viewed videos uploaded during 2019, which were &lt; 5 minutes long, and available in English or Spanish. We examined video content themes and speaker demographics. For patient education videos, we evaluated content understandability and quality of information using validated measures [i.e., Patient Education Materials Assessment Tool (PEMAT) and DISCERN]. Data was summarized using descriptive statistics. Results: A total of 31 of 64 clinical NCI-designated CC had dedicated YouTube pages. Only 6 (19%) CC had videos in languages other than English. A total of 402 videos were examined for content themes and demographic characteristics. 43% focused on patient education (n = 175), 36% research (n = 139), 24% survivorship (n = 95), and 13% clinical trials (n = 52). 32% (n = 119) of speakers were doctors and 18% (n = 65) patients. Perceived speakers’ ethnicity was 57% White (n = 229), followed by Asian (15%, n = 60), Black or African American (8%, n = 32), and Latinx (4%, n = 16). Perceived gender of speakers was 49% women (n = 197) and 51% men (n = 203). Most videos were understandable (91%, n = 159), but only 21% (n = 36) provided high quality information. Videos discussing treatments lacked discussion of risks, alternate options, and effects on quality of life. Conclusions: Most patient education videos uploaded to NCI-designated CC YouTube pages have low to moderate quality information and limited ethnic diversity of speakers. With ongoing trends of increasing misinformation spreading through social media, CC have an opportunity to create and disseminate high-quality, reliable, and comprehensive educational videos that meet the informational needs of patients with cancer and their caregivers.[Table: see text]
A reimbursement framework for artificial intelligence in healthcare
Authors: Michael D. Abràmoff, Cybil Roehrenbeck, Sylvia Trujillo, Juli Goldstein, Anitra S. Graves, Michael X. Repka, Ezequiel “Zeke” Silva III
Journal: npj Digital Medicine (2022)

Responsible adoption of healthcare artificial intelligence (AI) requires that AI systems which benefit patients and populations, including autonomous AI systems, are incentivized financially at a consistent and sustainable level. We present a framework for analytically determining value and cost of each unique AI service. The framework’s processes involve affected stakeholders, including patients, providers, legislators, payors, and AI creators, in order to find an optimum balance among ethics, workflow, cost, and value as identified by each of these stakeholders. We use a real world, completed, an example of a specific autonomous AI service, to show how multiple “guardrails” for the AI system implementation enforce ethical principles. It can guide the development of sustainable reimbursement for future AI services, ensuring the quality of care, healthcare equity, and mitigation of potential bias, and thereby contribute to realize the potential of AI to improve clinical outcomes for patients and populations, improve access, remove disparities, and reduce cost.
Effect of anticancer therapy on mortality and COVID-19 severity in cancer patients with COVID-19.
Authors: Phyo Thazin Myint, Aye Thet
Journal: Journal of Clinical Oncology (2022)

e22510 Background: Cancer patients are more susceptible to severe complications and high mortality from Coronavirus disease 2019 (COVID-19). There is no solid evidence of whether anti-cancer therapy plays a significant role in increasing COVID-19 severity or mortality in cancer patients. Also, there is no definitive US guideline on how to justify anti-cancer treatment in cancer patients with COVID-19. Therefore, we conducted a systematic review and meta-analysis of the effect of anti-cancer therapy in cancer patients infected with COVID-19. Methods: A systematic search of Pubmed and Cochrane databases was conducted and two reviewers screened the articles independently. Previously published review articles were also evaluated to include the studies not identified in the Pubmed and Cochrane. Any clinical study of adults was included if it contains data on mortality or COVID-19 severity in cancer patients, both treated and untreated within 3 months before COVID diagnosis. Pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated by employing the random-effects model, Mantel-Hazel method. Review Manager (RevMan) Version 5.4, The Cochrane Collaboration 2020 was used. Results: Out of 1690 studies identified from the databases and 8 studies from previous review articles, 22 studies (4777 patients) were included for analysis of the effect on mortality, and 12 studies (1898 patients) were included for the effect on COVID-19 severity. There were no significant differences in mortality between patients receiving anticancer treatment and those not (OR 1.17, 95% CI: [0.92-1.49], I2 = 56%, p = 0.21). There were no significant differences in mortality between patients receiving chemotherapy and those not receiving anticancer treatment but there was a trend towards higher mortality in patients receiving chemotherapy. (OR 1.43, 95% CI: [0.96-2.15], I2 = 68%, p = 0.08). There were no significant differences in COVID-19 severity between patients receiving anticancer treatment (OR 1.43, 95% CI: [0.96-2.15],, I2 = 10%, p = 0.27) and those not and between patients receiving chemotherapy and those not receiving anticancer treatment (OR 1.17, 95% CI: [0.83-1.65], I2 = 10%,p = 0.36). Conclusions: The results of our study were similar to previous meta-analyses despite more clearly defining anti-cancer treatment recency (anti-cancer treatment within 3 months before COVID diagnosis). There was low heterogeneity among studies for COVID-19 severity but high heterogeneity among studies for mortality. Most of the studies we analyzed were conducted in the 2020 and pre-vaccine era. Novel COVID-19 treatments and vaccination will likely affect outcomes in cancer patients with or without anti-cancer treatment. We need updated research and more detailed guidelines on anti-cancer therapy in COVID-19 infections.
The added value of histological subtype in the prediction of oncologic outcomes in patients with non-metastatic papillary renal cell carcinoma
Authors: G. Rosiello, G. Baiamonte, G. Fallara, G. Basile, R. Luciano, M. Colecchia, A. Martini, D. Cignoli, L. Nocera, F. Belladelli, G. Colandrea, D. Canibus, C. Re, G. Musso, F. Cei, A. Briganti, R. Bertini, A. Necchi, D. Raggi, P.I. Karakiewicz, F. Montorsi, A. Salonia, A. Larcher, U. Capitanio
Journal: European Urology (2022)
IMMU-11. Evaluation of CAR-T cells targeting CD276 in medulloblastoma
Authors: Patricia Benites Goncalves da Silva, Laura Sieber, Norman Mack, Daniel Atar, Lena M Kutscher, Patrick Schlegel, Martin Ebinger, Daisuke Kawauchi, Christian Seitz, Stefan M Pfister
Journal: Neuro-Oncology (2022)

Abstract Brain tumors are the most frequent category of solid tumors in children and have the highest mortality rate among all pediatric cancers. Although diagnosis and treatment have improved prognosis over the past decades for some childhood brain tumors, others remain lethal and current treatments are highly toxic to the developing brain, resulting in severe sequelae and considerably affecting the patient’s quality of life. Thus, new therapeutic options with reduced secondary effects are urgently needed. From this perspective, immunotherapies have gained a lot of attention due to their effectiveness in targeting tumor cells specifically. Chimeric-antigen receptor (CAR) T-cells recognize the target antigen on the surface of. CD276 is an immune checkpoint molecule that is expressed in a variety of solid tumor entities, including pediatric brain tumors. We analyzed the CD276 expression in our Patient-Derived-Xenograft (PDX) biobank of brain tumors and found that CD276 is ubiquitously expressed (ATRT, MB, EPN, GBM, ETMR, etc). Flow cytometry of MB PDX (n=4) confirmed CD276 expression of 97-99% of tumor cells, indicating that CD276 might be a good antigen target for CAR-T cell therapy of MBG3 and MBSHH. We found that second generation CAR-T cells targeting CD276 antigen significantly decreased tumor burden of the most aggressive MB subgroups (G3 and SHH-TP53mut PDX models) in NSG mice. We further treated NSG mice carrying a high tumor burden of the aggressive SHH-TP53mut PDX BT084 with second (CD28) and third generation (CD28-41BB) CD276-CAR-T cells. While both 2nd and 3rd generation improved the survival rates compared with CD19-CAR-T control cells, we found no difference in survival between the CD276 CAR-T generations, with no severe secondary effect during treatment. In conclusion, CD276 is a good antigen target for medulloblastoma, and warrants further evaluation for the treatment of medulloblastoma patients at relapse or as a maintenance therapy after standard treatment.